A review of the literature also found lower rates of cardiovascular events and mortality.
A statin combined with ezetimibe is more effective than statin monotherapy at lowering LDL cholesterol and reducing cardiovascular events, a meta-analysis has found.
Published in Mayo Clinic Proceedings, the paper analysed 14 studies involving nearly 110,000 patients, aged 67 on average. All had a history of hypercholesterolaemia and atherosclerotic cardiovascular disease, and all were either on statins alone or statins plus ezetimibe.
The team looked for change in mean LDL-C level as the primary outcome; secondary outcomes were risk of stroke, major cardiovascular events, cardiovascular and all-cause mortality, achievement of LDL-C under 1.8mmol/L, therapy discontinuation rate and adverse events.
Of the studies that measured change in mean LDL-C level, all but one found significantly greater reductions with combination therapy (the other found a non-significant reduction).
The effects on strokes, major events and mortality were less marked but overall favoured combination lipid-lowering therapy.
Pooled analysis found combination therapy led to a 0.34mmol/L greater reduction in LDL-C than statins alone.
There was a significant reduction in all-cause mortality of about 20% with combination treatment and a similar reduction in major cardiovascular events.
There was no statistically significant difference in cardiovascular mortality, side effects, discontinuation rates or achievement of the target LCL-C level.
When the intensity of the statins was considered, moderate-intensity statins alone and with ezetimibe had lower discontinuation rates than high-intensity statins.
Those on moderate statins with ezetimibe had an almost statistically significant 40% reduction in risk of myopathy compared with high-intensity statin alone, and moderate statins alone had a slightly lower risk than the combination.
“These results confirm that this [combination] approach should be recommended in patients at high to extremely high CVD risk, especially after an acute coronary syndrome,” the authors write.
They say an “an early and stringent approach to controlling LDL-C levels in very high-risk patient populations” is backed by the evidence.
“Based on the available data, lipid-lowering combination therapy facilitates the currently recommended approach of aggressive LDL-C lowering as evinced by the adages that ‘the lower the better and for longer’ and the equally important ‘the earlier the better’.”
The International Lipid Expert Panel recommends upfront combination therapy of statins and ezetimibe in very and extremely high-risk patients, and that the combination should be considered in those with an atherosclerotic CVD pre-event.
Ezetimibe is recommended in Australia for people who don’t reach target LDL-cholesterol on statin alone or who are intolerant to statins, the Heart Foundation’s chief medical advisor Professor Garry Jennings told TMR.
“Implicit in this recommendation is that statins and ezetimibe together are more effective in lowering LDL-C and hopefully major cardiovascular outcomes than a statin alone, as shown by this meta-analysis,” he said.
“The study authors hint at early use and perhaps initiation with the combination.
“This has not been formally tested both from a risk/benefit and health economics perspective. However, there is an analogy with hypertension management, where some international guidelines recommend initiating treatment with drug combinations rather than a single agent.”
